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How do Molecules form Living, Moving, Reproducing Cells? 1683, Leeuwenhoek: “An unbelievably great company of living animalcules, a-swimming more nimbly than any I had ever seen up to this time. The biggest sort bent their body into curves in going forwards." 1988, Francis Crick: “Every living cell and every biological macromolecule is the end result of natural selection, which had acted over billions of generations to produce complexity from ordinary physics and chemistry” Molecular Hierarchy of the Cell DNA → Proteins (Enzymes and Motors) → Protein Assemblies (Cytoskeletal Filaments) Moving Parts: Motor Proteins on Polymer Tracks Cellular Machines based on MTs and motors The Cilium The Mitotic Spindle “The Cell as a Collection of Protein Machines: Preparing the Next Generation of Molecular Biologists”. (Alberts, B (1998) Cell 92: 291). Protein Machine Motor Replication Machinery Helicase Transcription Machinery RNA polymerase Mitochondrial ATP synthase F1F0 ATPase Bacterial Flagellum Flagellar rotary motor Muscle Sarcomere Myosin-2 Lamellipodium Dendritic Actin Network Cilium MT motors Mitotic Spindle MTs and mitotic motors Assembly and Function? Biochemistry, Genetics, Microscopy, Quantitative Modeling. Bacterial (prokaryotic) Cells. Locomoting Eukaryotic Cells. Mechanism of Eukaryotic Cell Locomotion. Scanning E.M. of the leading edge. E.M. of Actin Filaments in the Leading Edge. Ribbon Diagram of Atomic Structure of Actin. Structure of Actin Filaments – helical symmetry. Actin Filament Assembly and Force Production. Actin filament polymerization drives Listeria Motility. Listeria Motility Julie Theriot Stanford University Medical School Eukaryotic Cell Reproduction; Mitosis and Cell Division. Mitosis studied in the Drosophila melanogaster Syncytial Embryo Sullivan Lab GFP-tubulin; histone-RFP; 480 seconds total time (Ingrid Brust-Mascher) MOTOR PROTEINS AND MICROTUBULE-BASED MACHINES. Mitosis in Drosophila Embryos. Mechanism of Mitosis. Metaphase Anaphase A Anaphase B Cytokinesis in Animal Cells.